👤 Venkata S Raman

Alzheimer disease (AD) biomarker and genetic testing results are increasingly disclosed to cognitively unimpaired adults in research and could in the future inform clinical treatment decisions in this population. To assess psychological outcomes after returning 3 categories of amyloid biomarker results as well as apolipoprotein E (APOE) genotypes. This cohort study was a secondary analysis of data collected as part of screening for the multisite AHEAD preclinical AD trial. Participants were individuals aged 55 to 80 years undergoing screening from July 14, 2020, to October 15, 2024. Participants were informed whether they had not-detected, intermediate, or elevated amyloid positron emission tomography levels, as well as their APOE genotype, which were categorized as noncarrier, ε4 heterozygote, or ε4 homozygote. Impact of Events Scale (IES; 15 items to assess intrusive thoughts and avoidance; each item is scored as not at all [0], rarely [1], sometimes [3], or often [5]; total range, 0-75), collected 24 to 72 hours after disclosure, and change in a scale measuring concerns about AD dementia (adapted scale using 6 items in which participants indicated their level of agreement with statements related to their perceived probability of developing AD dementia; items scored as strongly disagree [1] through strongly agree [5]; total range, 6-30), calculated by subtracting the score collected before biomarker testing from 1 collected after biomarker and genetic test results disclosure. Among 3414 included individuals, the mean (SD) age was 68.8 (6.0) years and 2116 (62%) were female. Group mean IES scores were below clinically significant thresholds. Nevertheless, across genetic groups, learning an elevated amyloid result (1184 participants) was associated with higher IES (mean [SD], 10.5 [10.9]) than intermediate amyloid (482 participants; mean [SD] IES, 8.8 [9.8]), and intermediate amyloid was associated with higher scores than not-detected amyloid (1748 participants; mean [SD] IES, 6.5 [8.4]). Across amyloid groups, learning APOE ε4 homozygosity (337 participants) was associated with higher mean (SD) IES (12.7 [11.6]) than heterozygosity (1609 participants; 9.1 [10.2]), and heterozygosity was associated with higher IES than noncarrier status (1468 participants; mean [SD] IES, 6.2 [8.1]). Both types of information were significant in an analysis of covariance model; no interaction effect was observed. In contrast, only biomarker disclosure was associated with differential change in concerns about AD dementia. Those with elevated amyloid showed a mean (SD) increase in concern (0.8 [3.5]), those with intermediate amyloid showed a smaller increase (0.4 [3.7]), and those with not-detected amyloid showed decreased concerns (-1.1 [4.2]). In this cohort study of cognitively unimpaired adults, associations with intrusive thoughts were observed to differ among genetic and biomarker subgroups; such associations were limited to biomarker subgroups for measures of perceived dementia risk. Show less

The genetic basis of sporadic early-onset Alzheimer's disease (EOAD) remains largely unknown, prompting evaluation of late-onset Alzheimer's disease (LOAD) polygenic risk in EOAD. A LOAD polygenic score (PGS) was calculated in the Longitudinal Early-onset Alzheimer's Disease Study (LEADS) and Alzheimer's Disease Neuroimaging Initiative (ADNI) study and tested for associations with AD risk, cognitive performance, and imaging and fluid biomarkers. Though PGS was elevated in LOAD and EOAD, it was not a significant predictor of EOAD adjusting for APOE ε4 carrier status and was not associated with age of EOAD onset (p = 0.106) or with cognitive performance (p = 0.417). In LEADS, greater LOAD PGS was associated with differences in neuroimaging and fluid biomarkers, including elevated synaptosomal-associated protein 25 (SNAP-25) (p = 2.3 × 10 While LOAD polygenic risk contributed minimally to EOAD onset and cognitive dysfunction, PGS association with fluid biomarkers in LEADS suggests a role for LOAD polygenic risk in EOAD pathophysiology. LOAD PGSs were elevated in both LOAD and EOAD compared to controls; however, LOAD PGS did not significantly predict EOAD risk, age at onset, or cognitive performance independent of APOE ε4 in the LEADS. Higher LOAD PGS was associated with lower amyloid PET Centiloids (less brain amyloid deposition) as well as lower CSF biomarker Aβ42 in LEADS (proxy marker suggesting higher brain amyloid deposition) in LEADS; these contradictory findings support the need for larger studies to further investigate whether LOAD PGS is associated with increased amyloid deposition in EOAD. Higher LOAD PGS was also associated with higher levels of CSF synaptosomal-associated protein 25 (SNAP-25), a key component of the SNARE complex, suggesting that LOAD genetic factors may contribute to dysregulation of synaptic transmission and/or pathological protein aggregation in EOAD. Show less

This study reported the profiling and the in-silico analysis of the therapeutic potential of proteins/peptides (for Alzheimer disease) isolated from Tinospora cordifolia, Evolvulus alsinoides, Centella asiatica and Convolvulus pluricaulis. The proteins/peptides were extracted by using four different pH based buffer solutions. The trypsin digested proteins/peptides were analyzed by LC-MS/MS based peptide mass fingerprinting which showed the presence of high number of proteins/peptides involved in regulating the oxidative stress. The sequential purification with 10 kDa and 3 kDa cut-off ultrafiltration membranes for buffer based extracted proteins/peptides was performed. The evaluation of crude and these filtrates revealed the highest antioxidant potential for 3 kDa cut-off filtrate of 0.1 M Tris HCl buffer (pH 8.0) from FRAP, DPPH, ABTS and NOS assays. The presence of peptides in 3 kDa cut-off filtrates was detected by HPLC, identified by MALDI-TOF MS and the fragmentation pattern was obtained by LC-MS/MS. The in-silico docking study revealed that the identified peptides showed the highest binding affinity against the Alzheimer targets (BACE1, nAChR, Aβ, AChE, GSK-3β, JNK). Thus, the findings of this study provided the preliminary evidence for the antioxidant and neuroprotective potential of the selected medicinal plants, by supporting their relevance in delaying the onset of neurodegeneration and highlighting their prospects for drug development. Show less

Retrospective cohort study of patients undergoing single-level L5-S1 anterior or transforaminal lumbar interbody fusion between 2012 and 2024 at a single academic institution, with preoperative and one-year postoperative radiographic assessment of sagittal alignment parameters. To quantify changes in lumbar pelvic angle (LPA), pelvic tilt (PT), global lumbar lordosis (L1-S1), regional lumbar lordosis (L4-S1), and segmental lumbar lordosis (L5-S1) among single-level L5-S1 ALIF and TLIF patients. Restoration of sagittal alignment is a primary goal of lumbar fusion. While ALIF is regarded as superior to TLIF in restoring segmental lordosis, its effect on global and regional alignment remains uncertain, and few studies directly compare their impact on spinopelvic parameters. The electronic medical record was queried for patients who underwent single-level L5-S1 ALIF or TLIF with preoperative and one-year postoperative imaging. Sagittal parameters were measured using Surgimap software. Group comparisons were assessed with unpaired t-tests or Wilcoxon signed-rank tests. Radiographic measurements were available for 174 patients (ALIF n=73, TLIF n=101). ALIF patients had significantly greater improvement in L4-S1 (+4.2° vs. -1.1°, P=0.002) and L5-S1 lordosis (+4.6° vs. -4.8°, P<0.001). No significant differences were observed in postoperative changes for L1-S1 lordosis (+2.2° vs. -1.4°, P=0.250), LPA (-1.9° vs. -1.4°, P=0.743), or PT (-0.9° vs. +0.4°, P=0.093). Permutation testing confirmed that the observed difference in LPA improvement between cohorts (-0.51°) was not statistically significant (P=0.673), and post hoc analysis confirmed adequate power to detect a difference of 3.37°. Sensitivity analyses using ANCOVA, adjusting for baseline radiographic values and covariates, were concordant. ALIF provided superior regional and segmental lordosis but did not improve global alignment compared with TLIF. This study is the first to quantify the effect of ALIF versus TLIF on LPA, highlighting the limited impact of single-level fusion on global spinopelvic alignment. Show less

Glucose-dependent insulinotropic peptide (GIP) is a 42-amino acid peptide hormone that regulates postprandial glucose levels. GIP binds to its cognate receptor, GIPR, and mediates metabolic physiology by improved insulin sensitivity, β-cell proliferation, increased energy consumption, and stimulated glucagon secretion. Dipeptidyl peptidase-4 (DPP4) catalyzes the rapid inactivation of GIP within 6 min Show less

Metabolic syndrome (MetS) amplifies the risks of atherosclerosis. Despite well-known sexual dimorphism in atherosclerosis, underlying mechanisms are poorly understood. Our previous findings highlight a proatherogenic protein, thrombospondin-1 (TSP-1), in hyperglycemia- or hyperleptinemia (mimicking obesity)-induced atherosclerosis. However, the role of TSP-1 in the development of atherosclerosis prompted by co-existing hyperglycemia and obesity, characteristic of MetS, is unknown. The goal of this study was to examine sex-specific differences in lesion progression in a model of combined MetS and atherosclerosis (KKAyApoE) and interrogate how these differences relate to TSP-1 expression. Male and female KKAy Metabolic profiling confirmed MetS phenotype of KKAy Together, the current study implicates a role of plasma testosterone in sex-specific differences in atherosclerosis and TSP-1 expression in MetS vs non-MetS mice. Our data suggest a sex-dependent differential role of TSP-1 on SMC de-differentiation in MetS. Collectively, these findings underscore a fundamental link between TSP-1 and VSMC phenotypic transformation in MetS. Show less